| Attributes | Values |
|---|
| rdf:type
| |
| Description
| - Long-term deregulated inflammation represents one of the key factors contributing to lung cancer eti-ology. Previously, we have observed that tumor necrosis factor- (TNF-), a major pro-inflammatorycytokine, enhances genotoxicity of benzo[a]pyrene (B[a]P), a highly carcinogenic polycyclic aromatichydrocarbon, in rat lung epithelial RLE-6TN cells, a model of alveolar type II cells. Therefore, we analyzedB[a]P metabolism in RLE-6TN cells under inflammatory conditions, simulated using either recombinant TNF-, or a mixture of inflammatory mediators derived from activated alveolar macrophage cell line.Inflammatory conditions significantly accelerated BaP metabolism, as evidenced by decreased levelsof both parent B[a]P and its metabolites. TNF- altered production of the metabolites associated withdihydrodiol-epoxide and radical cation pathways of B[a]P metabolism, especially B[a]P-dihydrodiols,and B[a]P-diones. We then evaluated the role of cytochrome P450 1B1 (CYP1B1), which is stronglyup-regulated in cells treated with B[a]P under inflammatory conditions, in the observed effects. ThesiRNA-mediated CYP1B1 knock-down increased levels of B[a]P and reduced formation of stable DNAadducts, thus confirming the essential role of CYP1B1 in B[a]P metabolism under inflammatory condi-tions. TNF- also reduced expression of aldo-keto reductase 1C14, which may compete with CYP1B1 forB[a]P-7,8-dihydrodiol and divert it from the formation of ultimate B[a]P dihydrodiol epoxide. Together,the present data suggests that the CYP1B1-catalyzed metabolism of polycyclic aromatic hydrocarbonsmight contribute to their enhanced bioactivation and genotoxic effects under inflammatory conditions.
- Long-term deregulated inflammation represents one of the key factors contributing to lung cancer eti-ology. Previously, we have observed that tumor necrosis factor- (TNF-), a major pro-inflammatorycytokine, enhances genotoxicity of benzo[a]pyrene (B[a]P), a highly carcinogenic polycyclic aromatichydrocarbon, in rat lung epithelial RLE-6TN cells, a model of alveolar type II cells. Therefore, we analyzedB[a]P metabolism in RLE-6TN cells under inflammatory conditions, simulated using either recombinant TNF-, or a mixture of inflammatory mediators derived from activated alveolar macrophage cell line.Inflammatory conditions significantly accelerated BaP metabolism, as evidenced by decreased levelsof both parent B[a]P and its metabolites. TNF- altered production of the metabolites associated withdihydrodiol-epoxide and radical cation pathways of B[a]P metabolism, especially B[a]P-dihydrodiols,and B[a]P-diones. We then evaluated the role of cytochrome P450 1B1 (CYP1B1), which is stronglyup-regulated in cells treated with B[a]P under inflammatory conditions, in the observed effects. ThesiRNA-mediated CYP1B1 knock-down increased levels of B[a]P and reduced formation of stable DNAadducts, thus confirming the essential role of CYP1B1 in B[a]P metabolism under inflammatory condi-tions. TNF- also reduced expression of aldo-keto reductase 1C14, which may compete with CYP1B1 forB[a]P-7,8-dihydrodiol and divert it from the formation of ultimate B[a]P dihydrodiol epoxide. Together,the present data suggests that the CYP1B1-catalyzed metabolism of polycyclic aromatic hydrocarbonsmight contribute to their enhanced bioactivation and genotoxic effects under inflammatory conditions. (en)
|
| Title
| - Inflammatory mediators accelerate metabolism of benzo[a]pyrene inrat alveolar type II cells: The role of enhanced cytochrome P450 1B1expression
- Inflammatory mediators accelerate metabolism of benzo[a]pyrene inrat alveolar type II cells: The role of enhanced cytochrome P450 1B1expression (en)
|
| skos:prefLabel
| - Inflammatory mediators accelerate metabolism of benzo[a]pyrene inrat alveolar type II cells: The role of enhanced cytochrome P450 1B1expression
- Inflammatory mediators accelerate metabolism of benzo[a]pyrene inrat alveolar type II cells: The role of enhanced cytochrome P450 1B1expression (en)
|
| skos:notation
| - RIV/00027162:_____/13:#0001051!RIV14-MZE-00027162
|
| http://linked.open...avai/riv/aktivita
| |
| http://linked.open...avai/riv/aktivity
| - I, P(GAP503/11/0142), Z(AV0Z50040702), Z(AV0Z50390703), Z(MZE0002716202)
|
| http://linked.open...iv/cisloPeriodika
| |
| http://linked.open...vai/riv/dodaniDat
| |
| http://linked.open...aciTvurceVysledku
| |
| http://linked.open.../riv/druhVysledku
| |
| http://linked.open...iv/duvernostUdaju
| |
| http://linked.open...titaPredkladatele
| |
| http://linked.open...dnocenehoVysledku
| |
| http://linked.open...ai/riv/idVysledku
| - RIV/00027162:_____/13:#0001051
|
| http://linked.open...riv/jazykVysledku
| |
| http://linked.open.../riv/klicovaSlova
| - Inflammation; CYP1B1; Polycyclic aromatic hydrocarbons; Metabolism; DNA adducts (en)
|
| http://linked.open.../riv/klicoveSlovo
| |
| http://linked.open...odStatuVydavatele
| |
| http://linked.open...ontrolniKodProRIV
| |
| http://linked.open...i/riv/nazevZdroje
| |
| http://linked.open...in/vavai/riv/obor
| |
| http://linked.open...ichTvurcuVysledku
| |
| http://linked.open...cetTvurcuVysledku
| |
| http://linked.open...vavai/riv/projekt
| |
| http://linked.open...UplatneniVysledku
| |
| http://linked.open...v/svazekPeriodika
| |
| http://linked.open...iv/tvurceVysledku
| - Svobodová, J.
- Machala, Miroslav
- Topinka, J.
- Vondráček, J.
- Neča, Jiří
- Schmuczerová, J.
- Kozubík, A.
- Šmerdová, L.
|
| http://linked.open...n/vavai/riv/zamer
| |
| issn
| |
| number of pages
| |
| http://bibframe.org/vocab/doi
| - 10.1016/j.tox.2013.09.001
|
![[RDF Data]](/fct/images/sw-rdf-blue.png)
![[cxml]](/fct/images/cxml_doc.png)
![[csv]](/fct/images/csv_doc.png)
![[text]](/fct/images/ntriples_doc.png)
![[turtle]](/fct/images/n3turtle_doc.png)
![[ld+json]](/fct/images/jsonld_doc.png)
![[rdf+json]](/fct/images/json_doc.png)
![[rdf+xml]](/fct/images/xml_doc.png)
![[atom+xml]](/fct/images/atom_doc.png)
![[html]](/fct/images/html_doc.png)